Research article summary (published 20 Jul 2009):

Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells.

Full Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in the body, however, they can be metabolized to more water-soluble products. Although they are more readily excreted than the parent compounds, some of the metabolites are still hydrophobic and may be more available to target tissues, such as the brain. They can also cross the placenta and reach a developing foetus. Much less is known about the toxicity of PCB metabolites than about the parent compounds. In the present study, we have investigated the effects of eight hydroxylated (OH) PCB congeners (2'-OH PCB 3, 4-OH PCB 14, 4-OH PCB 34, 4'-OH PCB 35, 4-OH PCB 36, 4'-OH PCB 36, 4-OH PCB 39, and 4'-OH PCB 68) on reactive oxygen species (ROS) formation and cell viability in rat cerebellar granule cells. We found that, similar to their parent compounds, OH-PCBs are potent ROS inducers with potency 4-OH PCB 14<4-OH PCB 36<4-OH PCB 34<4'-OH PCB 36<4'-OH PCB 68<4-OH PCB 39<4'-OH PCB 35. 4-OH PCB 36 was the most potent cell death inducer, and caused apoptotic or necrotic morphology depending on concentration. Inhibition of ERK1/2 kinase with U0126 reduced both cell death and ROS formation, suggesting that ERK1/2 activation is involved in OH-PCB toxicity. The results indicate that the hydroxylation of PCBs may not constitute a detoxification reaction. Since OH-PCBs like their parent compounds are retained in the body and may be more widely distributed to sensitive tissues, it is important that not only the levels of the parent compounds but also the levels of their metabolites are taken into account during risk assessment of PCBs and related compounds.

Author information

Author/s: Dreiem, Anne (A); Rykken, Sidsel (S); Lehmler, Hans-Joachim (HJ); Robertson, Larry W (LW); Fonnum, Frode (F);

Affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. axd17(-atsign-)health.state.ny.us

Grants: P42 ES013661 (Agency:NIEHS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol), published in United States. (Language: eng)

Reference: 2009-Oct; vol 240 (issue 2) : pp 306-13

Dates: Created 2009/09/28; Completed 2009/10/08;

PMID: 19631230, status: MEDLINE (last retrieved date: 10/8/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Animals, Newborn Antioxidants - pharmacology Apoptosis - drug effects Biotransformation Butadienes - pharmacology Cells, Cultured Cerebellum - drug effects; metabolism; pathology Dose-Response Relationship, Drug Environmental Pollutants - metabolism; toxicity Hydroxylation

Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Necrosis Nitriles - pharmacology Oxidative Stress - drug effects Polychlorinated Biphenyls - metabolism; toxicity Protein Kinase Inhibitors - pharmacology Rats Reactive Oxygen Species - metabolism Time Factors Vitamin E - pharmacology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Antioxidants (0) ; Butadienes (0) ; Environmental Pollutants (0) ; Nitriles (0) ; Polychlorinated Biphenyls (0) ; Protein Kinase Inhibitors (0) ; Reactive Oxygen Species (0) ; U 0126 (0) ; Vitamin E (1406-18-4) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.1.37) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.1.37)

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